HMP Shunt/Fructose & Galactose Metabolism Flashcards
What is the starting substrate > product of the Oxidative branch? What is the rate limiting enzyme, and what does it convert?
Glucose 6P > Ribose 5P
G6PD converts Glucose 6P > 6P Gluconolactone
What is the starting substrate > product of the Forward Non-oxidative branch? What is the enzyme used, and what does it convert?
Ribose 5P > Fructose 6P + Glyceraldehyde 3P
Transketolase converts Xylulose 5P > Fructose 6P + Glyceraldehyde 3P
What is the purpose of the Forward Non-oxidative branch?
Convert Ribose 5P to glycolytic intermediates (Fructose 6P and Glyceraldehyde 3P) when the body’s Ribose 5P needs are low - these glycolytic intermediates are eventually oxidized
What is the starting substrate > product of the Reverse Non-oxidative branch? What is the enzyme used, and what does it convert?
Fructose 6P + Glyceraldehyde 3P > Ribose 5P
Transketolase converts Fructose 6P + Glyceraldehyde 3P > Xylulose 5P
What is the purpose of the Reverse Non-oxidative branch?
Produce Ribose 5P when the body’s needs are high, without having to produce NADPH too (body’s needs for NADPH are low)
- Note: if the body needs both Ribose 5P and NADPH, it will use the Oxidative branch
What is the coenzyme utilized by Transketolase? What is Transketolase influenced by?
TPP
Influenced by substrate availability (no regulation)
What accumulates in the cytosol during the fed state and what does it lead to an accumulation of upstream? Why is this?
Citrate(cyto) accumulates - Citrate is an inhibitor of PFK-1 so this causes an accumulation of G6P (upstream of the PFK-1 step)
Where is accumulated G6P sent to and what does it help to produce?
G6P is shunted to the HMP Shunt where it produces NADPH via the Oxidative branch
What four processes require NADPH as an energy source?
- FA Synthesis
- Cholesterol Synthesis
- Steroid Synthesis
- Glutathione Reduction
In tissues with mitochondria, what source(s) is NADPH derived from? What about in tissues without mitochondria?
With mitochondria: Malic Enzyme and HMP Shunt
Without mitochondria: HMP Shunt only
What are the tissues without mitochondria?
- RBCs
- Cornea
- Lens
How does NADPH provide electrons for the reduction of hydrogen peroxide?
2 GSH (reduced) provide electrons to H2O2 to create two H2O > NADPH then provides electrons to convert GSSG (oxidized) back to GSH
G6PD uses NADP+ when it converts Glucose 6P to 6P Gluconolactone, which converts NADP+ back to NADPH
What are three major dietary sources of fructose?
- Disaccharide sucrose
- Free fructose in fruits, veggies, honey
- High fructose corn syrup
Is the entry of fructose into cells insulin-dependent?
NO, fructose metabolism is NOT insulin-dependent
What are the two steps in fructose metabolism? What are the enzymes used in each step?
- Fructose > Fructose 1P via Fructokinase
2. Fructose 1P > DHAP + Glyceraldehyde via Aldose B
What are DHAP and Glyceraldehyde converted into and what processes is this product used in?
DHAP + Glyceraldehyde > Glyceraldehyde 3P
Glyceraldehyde 3P is used in glycolysis and lipogenesis
Is the rate of fructose metabolism faster or slower than glucose metabolism and why?
Fructose metabolism is more rapid because it bypasses PFK-1, the rate-limiting step in glycolysis
How does high dietary fructose affect TAG synthesis?
High dietary fructose leads to high TAG synthesis via lipogenesis
What is the first step in galactose metabolism? What is the enzyme used in this step?
- Galactose > Galactose 1P via Galactokinase
What is the second step in galactose metabolism? What is the enzyme used in this step?
- Galactose 1P + UDP Glucose > UDP Galactose + Glucose 1P via Galactose 1P Uridyltransferase
What may UDP Galactose be converted to (third step of galactose metabolism) before it can proceed with metabolism? What is the enzyme used in this step?
UDP Galactose > UDP Glucose via UDP-Hexose 4-Epimerase
What is the fate of UDP Glucose produced in the third step of galactose metabolism?
UDP Glucose can…
- Participate in intermediary metabolism
- Convert another Galactose 1P into UDP galactose (second step)
What is the alternative fate of UDP Galactose produced from the second step of galactose metabolism?
UDP Galactose can be used to synthesize lactose, glycoproteins, glycolipids, and glycosaminoglycans
When galactose levels are continuously high due to galactose metabolism disorders, what enzyme converts galactose to an alcohol? What is the name of the this alcohol produced?
Galactose > Galactitol via Aldose Reductase
